title: Cellular and molecular response of human macrophages exposed to Aggregatibacter actinomycetemcomitans leukotoxin.
abstract: Aggregatibacter (Actinobacillus) actinomycetemcomitans is a facultative anaerobic gram-negative bacterium associated with severe forms of periodontitis. A leukotoxin, which belongs to the repeats-in-toxin family, is believed to be one of its virulence factors and to have an important role in the bacterium's pathogenicity. This toxin selectively kills human leukocytes by inducing apoptosis and lysis. Here, we report that leukotoxin-induced cell death of macrophages proceeded through a process that differs from the classical characteristics of apoptosis and necrosis. A. actinomycetemcomitans leukotoxin-induced several cellular and molecular mechanisms in human macrophages that led to a specific and excessive pro-inflammatory response with particular secretion of both interleukin (IL)-1β and IL-18. In addition, this pro-inflammatory cell death was inhibited by oxidized ATP, which indicates involvement of the purinergic receptor P2X(7) in this process. This novel virulence mechanism of the leukotoxin may have an important role in the pathogenic potential of this bacterium and can be a target for future therapeutic agents.
authors.affiliation: Division of Molecular Periodontology, Department of Odontology, Faculty of Medicine, Umeå University, Umeå, Sweden. peyman.kelk@odont.umu.se
authors.forename: P
authors.initials: P
authors.lastname: Kelk
authors.forename: H
authors.initials: H
authors.lastname: Abd
authors.forename: R
authors.initials: R
authors.lastname: Claesson
authors.forename: G
authors.initials: G
authors.lastname: Sandström
authors.forename: A
authors.initials: A
authors.lastname: Sjöstedt
authors.forename: A
authors.initials: A
authors.lastname: Johansson
mesh_terms: D000189:Actinobacillus Infections / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology; D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology* / Q000472:pathogenicity; D017209:Apoptosis; D001427:Bacterial Toxins / Q000276:immunology*; D002478:Cells, Cultured; D005098:Exotoxins / Q000276:immunology*; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000166:cytology* / Q000276:immunology; D014774:Virulence
chemical_list: D001427:Bacterial Toxins; D005098:Exotoxins; D020382:Interleukin-18; D053583:Interleukin-1beta; C018579:leukotoxin